Elizabeth O. Johnson

Mechanisms of stress: A dynamic overview of hormonal and behavioral homeostasis

Environmental events, both physical and emotional, can produce stress reactions to widely varying degrees. Stress can affect many aspects of physiology, and levels of stress, emotional status, and means of coping with stress can influence health and disease. The stress system consists of brain elements, of which the main components are the corticotropin-releasing hormone (CRH) and locus ceruleus (LC)-norepinephrine (NE)/autonomic systems, as well as their peripheral effectors, the pituitary-adrenal axis and the autonomic system, which function to coordinate the stress response. Activation of the stress system results in behavioral and physical changes which allow the organism to adapt. This system is closely integrated with other central nervous system elements involved in the regulation of behavior and emotion, in addition to the axes responsible for reproduction, growth and immunity. With current trends in stress research which focus on understanding the mechanisms through which the stress-response is adaptive or becomes maladaptive, there is a growing association of stress system dysfunction, characterized by hyperactivity and/or hypoactivity to various pathophysiological states. The purpose of this review is to 1) define the concepts of stress and the stress response from a historical perspective, 2) present a dynamic overview of the biobehavioral mechanisms that participate in the stress response, and 3) examine the consequences of stress on the physiologic and behavioral well-being of the organism by integrating knowledge from apparently disparate fields of science.

Nerve repair: Experimental and clinical evaluation of biodegradable artificial nerve guides

SUMMARY Several methods have been used for bridging nerve gaps. Much of the focus in nerve repair of peripheral nerves has focussed on creating either natural or synthetic tubular nerve guidance channels, as an alternative to nerve autografts. These conduits act to guide axons sprouting from the regenerating nerve end, provide a conduit for diffusion of neurotrophic and neurotropic factors secreted by the injured nerve stump, as well as help protect against infiltration of fibrous tissue. Among the conduits that have been studied are autogenous veins, arteries, mesothelial chambers, synthetic tubes, collagen tubes, amnion tubes, cardiac and skeletal muscle, and silicon tubes. This paper briefly reviews major studies in which bioabsorbable nerve guides were used for peripheral nerve repair, with a particular emphasis on polymeric guidance channels, in an effort to evaluate their use, their ability to support or enhance nerve regeneration and any potential problems.

Assessment of curve progression in idiopathic scoliosis

Abstract In a 5-year prospective study on idiopathic scoliosis, an attempt was made to elucidate the natural history of the disease and to determine which factors contribute to curve progression. A total of 85,622 children were examined for scoliosis in a prospective school screening study carried out in northwestern and central Greece. Curve progression was studied in 839 of the 1,436 children with idiopathic scoliosis of at least 10° detected from the school screening program. Each child was followed clinically and roentgenographically for one to four follow-up visits for a mean of 3.2 years. Progression of the scoliotic curve was recorded in 14.7% of the children. Spontaneous improvement of at least 5° was observed in 27.4% of them, with 80 children (9.5%) demonstrating complete spontaneous resolution. Eighteen percent of the patients remained stable, while the remaining patients demonstrated nonsignificant changes of less than 5° in curve magnitude. A strong association was observed between the incidence of progression and the sex of the child, curve pattern, maturity, and to a lesser extent age and curve magnitude. More specifically, the following were associated with a high risk of curve progression: sex (girls); curve pattern (right thoracic and double curves in girls, and right lumbar curves in boys); maturity (girls before the onset of menses); age (time of pubertal growth spurt); and curve magnitude (≥ 30°). On the other hand, left thoracic curves showed a weak tendency for progression. In conclusion, the findings of the present study strongly suggest that only a small percentage of scoliotic curves will undergo progression. The pattern of the curve according to curve direction and sex of the child was found to be a key indicator of which curves will progress.

Neuroanatomy of the brachial plexus: normal and variant anatomy of its formation

The brachial plexus is the complex network of nerves, extending from the neck to the axilla, which supplies motor, sensory, and sympathetic fibers to the upper extremity. Typically, it is formed by the union of the ventral primary rami of the spinal nerves, C5–C8 & T1, the so-called “roots” of the brachial plexus. By examining the neural architecture of the brachial plexus, the most constant arrangement of nerve fibers can be delineated, and the most predominate variations in the neural architecture defined. A thorough understanding of the neuroanatomy of the brachial plexus, with an appreciation of the possible anatomic variations that may occur is necessary for effective clinical practice.

Nerve repair : Experimental and clinical evaluation of neurotrophic factors in peripheral nerve regeneration

SUMMARY Neurotrophic factors are a family of polypeptides required for survival of discrete neuronal populations. In the normal state such factors are mostly synthesised by target tissues and are used for the viability of the nerve-cell bodies. After nerve injury, neurotrophic factors (NFs) are synthesised by non-neuronal (Schwann cells and fibroblasts) in the nerve trunk, and act to support the outgrowth of axons. NFs can be classified into three major groups: (1) neurotrophins; (2) neurokines; and (3) the transforming growth factor beta (TGF)-beta superfamily.

An update on recent advances in bone regeneration

SUMMARY Bone loss from trauma, neoplasia, reconstructive surgery and congenital defects remains a major health problem, making the development of effective bone regeneration therapies a primary priority. The long-term clinical goal is to reconstruct bony tissue in an anatomically functional three-dimensional morphology. Today, the science of bone regeneration is in its infancy with current and emerging therapies still having significant limitations. In addition to bone grafting, current bone regeneration strategies include the application of different bioactive factors, cell types, biologic or artificial scaffolds, alone or in various combinations. Recently, efforts are focused more on understanding the normal bone regenerative process where multiple factors interact in a defined temporal and spatial cascade of events. Bone biology has benefited over the last decade from an explosion of information regarding the molecular mechanisms underlying bone formation and resorption, as well as the feedback signals controlling these complex homeostatic mechanisms. New insights in the complexity of the homeostatic mechanisms regulating bone remodeling have uncovered potential therapeutic strategies for bone repair.

The Pterygopalatine Ganglion and its Role in Various Pain Syndromes: From Anatomy to Clinical Practice

Abstract  The postsynaptic fibers of the pterygopalatine or sphenopalatine ganglion (PPG or SPG) supply the lacrimal and nasal glands. The PPG appears to play an important role in various pain syndromes including headaches, trigeminal and sphenopalatine neuralgia, atypical facial pain, muscle pain, vasomotor rhinitis, eye disorders, and herpes infection. Clinical trials have shown that these pain disorders can be managed effectively with sphenopalatine ganglion blockade (SPGB). In addition, regional anesthesia of the distribution area of the SPG sensory fibers for nasal and dental surgery can be provided by SPGB via a transnasal, transoral, or lateral infratemporal approach. To arouse the interest of the modern‐day clinicians in the use of the SPGB, the advantages, disadvantages, and modifications of the available methods for blockade are discussed.▪

Strontium-90 concentration measurements in human bones and teeth in Greece.

Strontium-90 concentration was measured in human bones and teeth collected in Greece during the period 1992-1996. One hundred and five bone samples, mainly cancellous bone, and 108 samples, taken from a total of 896 individual teeth were processed. Samples were classified according to the age and sex of the donors. Samples were chemically pre-treated according to a specially devised method to enable extraction of 90Y, at equilibrium with 90Sr in the original sample. Subsequently, 90Y beta activity was measured with a gas proportional counter. Radiostrontium concentration in bone samples showed small variations with respect to age or sex, with an average value of 30 mBq 90Sr/g Ca. However, 90Sr concentration measurements in teeth demonstrated a pronounced structure, which clearly reflects contamination from the 1960s atmospheric nuclear weapons tests and the more recent Chernobyl accident. This difference is attributed to the different histological structure of skeletal bones and teeth, the later consisting mainly of compact bone. An age-dependent model for radiostrontium concentration in human bones and teeth is developed which is able to successfully reproduce the experimental data. Through a fitting process, the model also yielded calcium turnover rates for compact bone, as a function of age, as well as an estimate of radiostrontium contamination of foodstuffs in Greece for the past four decades. The results obtained in this study indicate that radiostrontium environmental contamination which resulted from the atmospheric nuclear weapons tests in the 1960s, exceed by far that caused by the Chernobyl accident.

Effects of early parenting on growth and development in a small primate

We report here a study of the impact of caregiver-infant relationships on physical growth and behavioral development in a small primate, the common marmoset. Somatic growth was assessed from measurements of body weight, knee-heel length, head-tail length, head circumference, and pudendal pad width in females or testis volume in males obtained from unanesthetized monkeys. Behavioral information was gathered by focal animal samples for discrete rearing behaviors. Our data suggest that the frequency of positive parental behaviors during infancy is correlated with stature when the monkeys reach 10 and 20 wk of age. Furthermore, we found that juveniles that were mistreated by their parents during infancy were smaller in body weight, knee-heel length, and head-tail length, and they demonstrated abnormal social behavior. Finally, to address whether the apparent decreased growth observed in the young animals that had experienced negative parenting was also associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis function, we examined the plasma ACTH and cortisol responses to synthetic ovine corticotropin-releasing hormone(oCRH) in these animals. We found that the incremental cortisol response to exogenous oCRH was significantly lower in the young adults that had experienced negative parenting during infancy compared with those who had nonabusive parents, indicating altered hypothalamic-pituitary-adrenal axis function in these animals. Our findings suggest that the quality of parental care influences later growth and behavior in the young marmoset.

PRIMARY CORTISOL RESISTANCE: A FAMILIAL SYNDROME AND AN ANIMAL MODEL

Primary cortisol resistance in man is a familial disease. It is characterized by increased plasma cortisol concentrations, high urinary free cortisol excretion, a normal circadian pattern of cortisol secretion, resistance to adrenal suppression by dexamethasone and absence of clinical stigmata of Cushings syndrome. In its severe form, hypertension and hypokalemic alkalosis are present, owing to increased secretion of the sodium-retaining corticoids, corticosterone and deoxycorticosterone. In subjects with a less severe resistance to cortisol, there are no clinical abnormalities and the disease is revealed only by detailed examination of several parameters of cortisol metabolism. In the whole-cell assay (peripheral mononuclear leukocytes or fibroblasts) the glucocorticoid receptor shows a low affinity for dexamethasone. The receptor may be unsaturable as suggested by decreased receptor concentrations in broken-cell systems. Thus, generalized target-tissue resistance to cortisol, including the pituitary gland and the hypothalamus, is accompanied by a decreased negative feedback of the cortisol-ACTH feedback system resulting in increased ACTH secretion. This causes higher plasma cortisol to compensate for the end-organ resistance and also increases the production of adrenal mineralocorticoids, as by-products. Thus hypertension and hypokalemic alkalosis depends on the degree of the resistance. Cortisol resistance in many New World primate species is characterized by greatly increased plasma cortisol concentrations, decreased cortisol binding globulin capacity and affinity, high levels of plasma and urinary free cortisol, marked resistance of ACTH suppression by dexamethasone, and no physiologic evidence of glucocorticoid hormone excess. Target tissues have normal concentrations of glucocorticoid receptors with decreased affinity for dexamethasone. The New World primates, unlike man, have compensated for this cortisol resistance with intra-adrenal adaptations over the 50 million years of their evolutionary development. These primates also have abnormalities of other steroid hormone-receptor systems such as progesterone, estrogen, androgen and mineralocorticoid. In contrast, the human syndrome appears to be a recent mutation with pathophysiologic consequences.